N¹-(4-acetylphenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride | 1375736-82-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N¹-(4-acetylphenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride
• 英文别名: N1-(3,4-difluorophenyl)-N2-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride；N-(4-acetylphenyl)-N'-[[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]-piperidin-2-ylmethyl]oxamide;hydrochloride
• CAS: 1375736-82-5
• 化学式: C₂₁H₂₆N₄O₄S*ClH
• 分子量: 466.989
• InChiKey: DXLXRYOSDAPPHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4-乙酰基苯基)氨基甲酰甲酸乙酯 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 N¹-(4-acetylphenyl)-N²-((5-(hydroxymethyl)-4-methylthiazol-2-yl)(piperidin-2-yl)methyl)oxalamide hydrochloride
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1

  摘要：

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.

  DOI：

  10.1021/jm3002247